BACKGROUND: We recently reported that the efficacy of nitric oxide (NO) appears to be based on both sex and hormone status. The mechanism responsible for this differential efficacy is unknown. The aim of this study was to characterize the effect of sex, hormones, and NO on the extracellular signal-regulated kinase (ERK) and Akt signaling pathways after arterial injury. METHODS: Male and female Sprague-Dawley rats underwent castration or sham surgery. Two weeks later, they underwent carotid artery balloon injury. Treatment groups included the following: control, injury, and injury + 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) (n = 5 per group). Arteries were harvested 2 weeks after injury and assessed for phospho-ERK (pERK) and phospho-Akt (pAkt) expression. RESULTS: After injury, more pERK and pAkt activity was seen in the adventitia than media in both sexes, regardless of hormone status (P < .05). In hormonally intact males, NO further increased pERK (44%) and pAkt (120%) after injury (P < .001). Castration attenuated the effects of NO. In hormonally intact females, NO caused the opposite pattern with pERK activity but did not affect pAkt activity. CONCLUSIONS: After arterial injury, ERK and Akt activity is significantly greater in the adventitia than the media, and depends on sex, hormone status, and NO. Understanding adventitial regulation of proliferative signaling pathways will allow the development of targeted therapies for neointimal hyperplasia.
BACKGROUND: We recently reported that the efficacy of nitric oxide (NO) appears to be based on both sex and hormone status. The mechanism responsible for this differential efficacy is unknown. The aim of this study was to characterize the effect of sex, hormones, and NO on the extracellular signal-regulated kinase (ERK) and Akt signaling pathways after arterial injury. METHODS: Male and female Sprague-Dawley rats underwent castration or sham surgery. Two weeks later, they underwent carotid artery balloon injury. Treatment groups included the following: control, injury, and injury + 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) (n = 5 per group). Arteries were harvested 2 weeks after injury and assessed for phospho-ERK (pERK) and phospho-Akt (pAkt) expression. RESULTS: After injury, more pERK and pAkt activity was seen in the adventitia than media in both sexes, regardless of hormone status (P < .05). In hormonally intact males, NO further increased pERK (44%) and pAkt (120%) after injury (P < .001). Castration attenuated the effects of NO. In hormonally intact females, NO caused the opposite pattern with pERK activity but did not affect pAkt activity. CONCLUSIONS: After arterial injury, ERK and Akt activity is significantly greater in the adventitia than the media, and depends on sex, hormone status, and NO. Understanding adventitial regulation of proliferative signaling pathways will allow the development of targeted therapies for neointimal hyperplasia.
Authors: T Couffinhal; P Dufourcq; B Jaspard; D Daret; C Allières; P Alzieu; P Serre; J Bonnet; C Duplàa Journal: Coron Artery Dis Date: 2001-12 Impact factor: 1.439
Authors: R C Braun-Dullaeus; M J Mann; U Seay; L Zhang; H E von Der Leyen; R E Morris; V J Dzau Journal: Arterioscler Thromb Vasc Biol Date: 2001-07 Impact factor: 8.311
Authors: Melissa E Hogg; Vinit N Varu; Ashley K Vavra; Daniel A Popowich; Monisha N Banerjee; Janet Martinez; Qun Jiang; Joseph E Saavedra; Larry K Keefer; Melina R Kibbe Journal: Free Radic Biol Med Date: 2011-01-21 Impact factor: 7.376
Authors: William S Weintraub; Stephen D Clements; L Van-Thomas Crisco; Robert A Guyton; Joseph M Craver; Ellis L Jones; Charles R Hatcher Journal: Circulation Date: 2003-03-11 Impact factor: 29.690
Authors: Elena A Goncharova; Alaina J Ammit; Carla Irani; Richard G Carroll; Andrew J Eszterhas; Reynold A Panettieri; Vera P Krymskaya Journal: Am J Physiol Lung Cell Mol Physiol Date: 2002-08 Impact factor: 5.464